Balloon catheter with flexible electrode assemblies

ABSTRACT

In some implementations, a method of ablating body tissue includes (a) locating an inflatable balloon portion of a cryotherapy balloon catheter at a treatment site internal to a patient&#39;s body, and inflating the inflatable balloon portion; (b) employing electrodes that are disposed on an expandable surface of the inflatable balloon portion to electrically characterize body tissue at the treatment site; (c) ablating the body tissue by supplying a cryotherapy agent to the inflatable balloon portion to cool the body tissue to a therapeutic temperature; (d) employing the electrodes to determine whether the ablating caused desired electrical changes in the body tissue; and (e) repeating (c) and (d) when it is determined that the ablating did not cause the desired electrical changes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/413,533, filed Mar. 6, 2012, now U.S. Pat. No. 9,060,756, which is acontinuation of U.S. patent application Ser. No. 12/127,287, filed May27, 2008, now U.S. Pat. No. 8,128,617 the entire disclosures of whichare all incorporated herein by reference.

TECHNICAL FIELD

A balloon catheter for electrical mapping and cryo ablation is generallydescribed.

BACKGROUND

A number of serious medical conditions may be treated in a minimallyinvasive manner with various kinds of catheters designed to reachtreatment sites internal to a patient's body. One such medical conditionis atrial fibrillation—a serious medical condition that results fromabnormal electrical activity within the heart. This abnormal electricalactivity may originate from various focal centers of the heart andgenerally decreases the efficiency with which the heart pumps blood. Itis believed that some of these focal centers reside in the pulmonaryveins of the left atrium. It is further believed that atrialfibrillation can be reduced or controlled by structurally altering orablating the tissue at or near the focal centers of the abnormalelectrical activity.

One method of ablating tissue of the heart and pulmonary veins tocontrol atrial fibrillation includes delivering radiofrequency (RF)energy to the tissue to be ablated. In particular, high frequency energycan be employed, for example, to cause ionic agitation and frictionalheat in targeted tissue, causing permanent damage to the tissue. Oncedamaged, the tissue may no longer propagate or source electricalsignals, and the fibrillation may be treated or reduced. The RF energycan be delivered by an RF catheter having an RF source at a distaltreatment end that is positioned at a treatment site inside a patientduring a treatment procedure.

Another method of ablating tissue of the heart and pulmonary veins tocontrol atrial fibrillation is through cryotherapy, or the extremecooling of body tissue. Cryotherapy may also cause permanent alterationto treated tissue, preventing the treated tissue from propagating orsourcing electrical signals, thereby reducing or eliminating atrialfibrillation. Cryotherapy may be delivered to appropriate treatmentsites inside a patient's heart and circulatory system by a cryotherapycatheter. A cryotherapy catheter generally includes a treatment memberat its distal end, such as an expandable balloon having a coolingchamber inside. A cryotherapy agent may be provided by a source externalto the patient at the proximal end of the cryotherapy catheter anddelivered distally through a lumen in an elongate member to the coolingchamber where it is released. Release of the cryotherapy agent into thechamber cools the chamber, the balloon's outer surface, and tissue thatis in contact with the outer surface, to perform ablation. Thecryotherapy agent may be exhausted proximally through an exhaust lumenin the elongate member to a reservoir external to the patient.

In addition to facilitating permanent tissue alteration, cryotherapyfacilitates temporary electrical inactivation of tissue in a manner thatenables a physician to test the likely results of ablation through areversible process. Such a process is commonly referred to ascryomapping, and generally involves cooling tissue to near freezing(e.g., to 0° C.) but well above a temperature at which the tissue wouldbe ablated (e.g., −20° C.).

It may be advantageous to map the electrical activity of a pulmonaryvein (or other treatment site) prior to permanent ablation by either RFor cryotherapy, in order to pinpoint appropriate ablation target sites.Some apparent target sites may not actually contribute to abnormalelectrical activity, and treating such sites may not be desirable.Treating other target sites may affect healthy tissue in undesirableways (e.g., creating conduction blocks). Precisely mapping theelectrical activity in a target treatment region can help focus thetreatment and confirm its efficacy and safety.

Various specialized mapping catheters may be employed to electricallymap tissue, such as a circular catheter or a multi-electrode basketcatheter. Such mapping catheters can be positioned at possible treatmentsites inside a patient, and electrodes at those sites can providesignals to a processing system external to the patient that can processthe signals and provide physicians with information to subsequentlyposition a separate RF or cryotherapy catheter and deliver with thatseparate catheter appropriately targeted ablation energy.

SUMMARY

In some implementations, an inflatable distal balloon portion of acryotherapy balloon catheter includes electrodes on its expandablesurface that can enable a single balloon catheter to be used to bothelectrically map a potential treatment site inside a patient's body andprovide cryotherapy to the treatment site. In operation, the distalballoon portion can be located at a treatment site internal to apatient's body and inflated; the electrodes can be employed toelectrically characterize body tissue at the treatment site; when theelectrical characterization indicates that ablation is appropriate forthe body tissue at the treatment site, cryotherapy can be delivered tothe treatment site (e.g., a cryogenic agent can be delivered to thedistal balloon portion); and following cryotherapy delivery, theelectrodes can be employed to again characterize the body tissue at thetreatment site to confirm that the electrical properties of the bodytissue were altered by the cryotherapy in a desirable manner. Throughoutthe electrical characterization and cryotherapy treatment, the distalballoon portion may remain at a fixed location. That is, electricalcharacterization (at two or more different times), and cryotherapydelivery, can be performed without moving the cryotherapy catheter, onceit is initially positioned.

In some implementations, the distal balloon portion includes more thanone inflatable balloons, such that at least one balloon forms a safetychamber to protect body tissue in the event that one balloon ruptures oris otherwise compromised. In multi-balloon implementations, electrodescan be disposed on a balloon other than the outermost balloon. Forexample, electrodes code be disposed on an inner safety balloon, and amaterial for the outer balloon could be selected such that goodelectrical contact is provided between electrodes on the safety balloonand body tissue adjacent to the electrodes and in contact to theexternal surface of an outer balloon.

In some implementations, the body tissue can be electricallycharacterized during the cryotherapy treatment. Moreover, thecryotherapy treatment may be broken into two phases: a first mappingphase, during which body tissue is only temporarily altered (e.g., bycooling the body tissue to a first temperature) to confirm thelikelihood that permanent treatment will be efficacious; and a secondtreatment phase, during which the body tissue can be permanently altered(e.g., by cooling the body tissue to a second temperature that is lowerthan the first temperature).

In some implementations, some electrodes can also be used to stimulatebody tissue (e.g., during the first phase) and other electrodes can beused to detect stimulation signals. For example, by providing anelectrical stimulus signal at one electrode, and detecting the signal atone or more other electrodes, body tissue may be electricallycharacterized in the absence of electrical signals generated by the bodytissue itself. Such stimulus-based tissue characterization may beadvantageous at various points of therapy, including before, during orafter cryotherapy is delivered, and the characterization may be usefulin determining whether particular regions of body tissue are goodcandidates for cryotherapy, or whether previously administeredcryotherapy has caused its intended effect.

The details of one or more implementations are set forth in theaccompanying drawings and the description below. Other features,objects, and advantages will be apparent from the description anddrawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram of an example cryotherapy catheter having aninflatable balloon portion that can be employed to electricallycharacterize body tissue and deliver cryotherapy to the body tissue.

FIGS. 2A-2D illustrate additional details of internal structures of theinflatable balloon portion that is shown in FIG. 1.

FIG. 3 illustrates example details of the electrodes that can bedisposed on the surface of the inflatable balloon of FIG. 1.

FIG. 4 illustrates additional example details of the electrodes that areshown in FIG. 3.

FIGS. 5A-5D illustrate example electrical signals that can be obtainedfrom the electrodes shown in FIGS. 3 and 4 to electrically characterizebody tissue that is contact with the inflatable balloon of FIG. 1.

FIGS. 6A and 6B illustrate another example configuration of electrodeson the surface of the inflatable balloon of FIG. 1.

FIG. 7 illustrates example splines that can be employed in conjunctionwith the inflatable balloon of FIG. 1.

FIG. 8 illustrates an example structure on the splines shown in FIG. 7,which can be employed to help collapse the inflatable balloon.

FIGS. 9A-9C illustrate example spline configurations.

FIG. 10 is an example cross-section of the inflatable balloon portionshown in FIGS. 1 and 3.

FIGS. 11 A-1 1C illustrate example electrodes that can be included withthe inflatable balloon of FIG. 1.

FIGS. 12A-12D illustrate another example spline and electrode structure.

FIG. 13 illustrates an example wiring scheme for electrodes that canreinforce a shaft of the cryotherapy catheter shown in FIG. 1.

FIG. 14 is flow diagram of an example method of treating body tissuewith the cryotherapy catheter shown in FIG. 1.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

FIG. 1 is a diagram of an example cryotherapy catheter 100 that can beemployed to electrically characterize body tissue and delivercryotherapy to the body tissue. As shown in one implementation, thecryotherapy catheter 100 includes a distal inflatable balloon portion103 that can be routed to a treatment site inside a patient toelectrically characterize and deliver cryotherapy to that treatmentsite; a proximal end 106 that remains outside a patient during treatmentand facilitates connection of various equipment to the cryotherapycatheter; and an elongate member 109 that couples the proximal-endequipment to the distal inflatable balloon portion.

The distal inflatable balloon portion 103 includes a number ofelectrodes 112 on its expandable surface 118 that can be employed toelectrically characterize tissue that is contact with the electrodes 112at the treatment site. In particular, for example, the electrodes can beconfigured to support a detailed intracardiac electrophysiology study.Other types of electrodes or sensors can also be included on or near thesurface 118 of the balloon 103, such as, for example, thermal orpressure sensors. As is described in more detail below, the distalinflatable balloon portion 103 can include more than one balloon. Forexample, a second safety balloon can be included inside an outer balloonto isolate body fluids from the inside of the balloon 103 portion, andto isolate therapy agents inside the balloon portion 103 form bodytissue, in the event that the integrity of one of the balloons iscompromised. In such multi-balloon implementations, the electrodes 112can be disposed on an inner balloon, and the outer balloon can beconstructed to facilitate appropriate electrical contact between theelectrodes and body tissue, through the outer balloon.

The catheter's elongate member 109 has multiple internal lumens (notshown in FIG. 1). The lumens allow cryogenic fluid to be delivereddistally from an external cryogenic fluid source 121 to an internalchamber of the balloon 103. In addition, the internal lumens of theelongate member 109 allow exhaust resulting from delivery of cryogenicfluid to the internal chamber of the balloon 103 to be deliveredproximally from the internal chamber to an external exhaust pump 124.During operation, there may be continuous circulation within theelongate member 109 of cryogenic fluid distally and exhaust proximally.The elongate member 109 also includes conductors (not shown) that carryelectrical signals from the electrodes 112 to a signal processor 127 atthe proximal end of the catheter 100.

The signal processor 127 can process the electrical signals toelectrically characterize body tissue that is in contact with theelectrodes. In particular, the signal processor 127, in someimplementations, generates visual displays, such as isochronal orisopotential maps of the tissue, which a physician may use to identifyaberrant electrical pathways at locations in the body tissue that may becandidates for ablation. The visual displays may be provided in a userinterface 130 (e.g., a flat panel display, or other suitable outputdevice). Example displays are described further below, with reference toFIGS. 5A-5D.

The signal processor 127 can include circuitry for receivingbiopotential signals (e.g., differential amplifiers or other amplifiersthat sense biopotential signals and amplify them to levels that can beused in further processing) and processing the signals in a manner thatpermits their subsequent analysis, for example by a medical professionaldelivering or considering delivering cryotherapy to a patient. Thesignal processor 127 can also include circuitry for generatingstimulation signals that may be routed to one or more of the electrodes112. For example, in some implementations, it is advantageous tostimulate portions of tissue with one or more electrodes and measure theelectrical effect of such stimulation with one or more other adjacent ornearby electrodes. In this manner, aberrant electrical pathways may beidentified, even if a source of electrical impulses that would travelover the aberrant electrical pathways is not active when the tissue isanalyzed.

In some implementations, the signal processor 127 includes dedicatedcircuitry (e.g., discrete logic elements and one or moremicrocontrollers; application-specific integrated circuits (ASICs); orspecially configured programmable devices, such as, for example,programmable logic devices (PLDs) or field programmable gate arrays(FPGAs)) for processing biopotential signals and displaying a graphicalrepresentation of the signals in a user interface. In someimplementations, the signal processor 127 includes a general purposemicroprocessor and/or a specialized microprocessor (e.g., a digitalsignal processor, or DSP, which may be optimized for processinggraphical or a biometric information) that executes instructions toreceive, analyze and display information associated with the receivedbiopotential signals. In such implementations, the signal processor 127can include program instructions, which when executed, perform part ofthe signal processing. Program instructions can include, for example,firmware, microcode or application code that is executed bymicroprocessors or microcontrollers. The above-mentioned implementationsare merely exemplary, and the reader will appreciate that the signalprocessor 127 can take any suitable form.

A controller 133 at the proximal end can regulate flow of cryogenicfluid to the internal chamber of the balloon 103 and flow of exhaustfrom the balloon 103. In particular, for example, the controller 133can, in one implementation as shown, regulate a valve 136 that controlsflow of the cryogenic fluid from the cryogenic fluid source 121. Thecryogenic fluid source 121 may be, for example, a pressured flask ofcryogenic fluid. In other implementations (not shown), the controllercontrols a pump and/or pump valve combination to deliver cryogenic fluidto the internal chamber of the balloon. Similarly, the controller 133can regulate a valve 139 and/or external exhaust pump 124 to regulateflow of exhaust from the internal chamber of the balloon.

By controlling both the rate at which cryogenic fluid is delivered tothe balloon 103 and the rate at which exhaust is extracted from theballoon 103, the controller 133 can develop and maintain a pressureinside the balloon 103 at a number of different values. For example,when cryogenic fluid is delivered at a very low rate to the balloon 103,and exhaust is similarly extracted at a very low rate, the balloon 103may be inflated, but very little heat (if any) may be extracted from theballoon 103 or from body tissue that is in contact with the balloon'ssurface 118. As another example, when cryogenic fluid is delivered at ahigher rate, heat can be extracted from the balloon 103 and from bodytissue that is in contact with the balloon 103. Varying the rate atwhich exhaust is extracted from the balloon 103 relative to the rate atwhich the cryogenic fluid is supplied to the balloon can control thepressure inside the balloon 103. In particular, for example, for a givenrate at which the cryogenic fluid is supplied to the balloon, a greaterrate at which exhaust is extracted from the balloon 103 will generallyresult in lower pressure inside the balloon, and a lower rate at whichexhaust is extracted from the balloon 103 will generally result ingreater pressure inside the balloon.

To precisely control pressures or flow rates, the controller 133 mayemploy either or both of open- or closed-loop control systems. Forexample, in some implementations, a rate at which cryogenic fluid (e.g.,the position of the valve 136) may be controlled with an open-loopcontrol system, and a rate at which exhaust is extracted from theballoon 103 (e.g., the position of the valve 139, or the pressureexerted by the pump 124) may be controlled with a closed-loop controlsystem. In other implementations, both rates may be controlled byclosed-loop control systems. In a closed-loop control system, somefeedback mechanism is provided. For example, to control the rate atwhich exhaust is extracted from the balloon 103, the controller 133 mayemploy an exhaust flow sensor device (not shown), a pressure sensor (notshown) inside the balloon 103 or elsewhere in the system, or anotherfeedback sensor. In addition, the controller 133 may employ an ambientpressure gauge 142 in one of its control loops (e.g., to measureatmospheric pressure at the proximal end 106 of the cryotherapy catheterthat remains outside the patient).

In some implementations, as mentioned above, pressure inside the balloon103 may be primarily controlled by controlling the rate at which exhaustis extracted from the balloon 103 (given the significant differencebetween the large volume of gas resulting from a corresponding smallervolume of cryogenic fluid being released into the balloon 103).Temperature inside the balloon 103, on the other hand, may depend oncontrol of both the flow of cryogenic fluid and the flow of exhaust.

The controller 133 itself can take many different forms. In someimplementations, the controller 133 is a dedicated electrical circuitemploying various sensors, logic elements and actuators. In otherimplementations, the controller 133 is a computer-based system thatincludes a programmable element, such as a microcontroller ormicroprocessor, which can execute program instructions stored in acorresponding memory or memories. Such a computer-based system can takemany forms, include many input and output devices (e.g., the userinterface 130 and other common input and output devices associated witha computing system, such as keyboards, point devices, touch screens,discrete switches and controls, printers, network connections, indicatorlights, etc.) and may be integrated with other system functions, such asmonitoring equipment 145 (described in more detail below), a computernetwork, other devices that are typically employed during a cryotherapyprocedure, etc. For example, a single computer-based system may includea processor that executes instructions to provide the controllerfunction, display imaging information associated with a cryotherapyprocedure (e.g., from an imaging device); display pressure, temperatureand time information (e.g., elapsed time since a given phase oftreatment was started); and serve as an overall interface to thecryotherapy catheter. In general, various types of controllers arepossible and contemplated, and any suitable controller 133 can beemployed. Moreover, in some implementations, the controller 133 and thesignal processor 127 may be part of a single computer-based system, andboth control and signal processing functions may be provided, at leastin part, by the execution of program instructions in a singlecomputer-based system.

The catheter 100 shown in FIG. 1 is an over-the-wire type catheter. Sucha catheter 100 uses a guidewire 148, extending from the distal end ofthe catheter 100. In some implementations, the guidewire 148 may bepre-positioned inside a patient's body; once the guidewire 148 isproperly positioned, the balloon 103 (in a deflated state) and theelongate member 109 can be routed over the guidewire 148 to a treatmentsite. In some implementations, the guidewire 148 and balloon portion 103of the catheter 100 may be advanced together to a treatment site insidea patient's body, with the guidewire portion 148 leading the balloon 103by some distance (e.g., several inches). When the guidewire portion 148reaches the treatment site, the balloon 103 may then be advanced overthe guidewire 148 until it also reaches the treatment site. Otherimplementations are contemplated, such as steerable catheters that donot employ a guidewire. Moreover, some implementations include anintroducer sheath that can function similar to a guidewire, and inparticular, that can be initially advanced to a target site, after whichother catheter portions can be advanced through the introducer sheath.

The catheter 100 can include a manipulator (not shown), by which amedical practitioner may navigate the guidewire 148 and/or balloon 103through a patient's body to a treatment site. In some implementations,release of cryogenic fluid into the cooling chamber may inflate theballoon 103 to a shape similar to that shown in FIG. 1. In otherimplementations, a pressure source 154 may be used to inflate theballoon 103 through an inflation lumen 156, independently of the releaseof cryogenic fluid into the internal chamber of the balloon 103. Thepressure source 154 may also be used to inflate an anchor member on theend of the guidewire 148 (not shown).

The catheter 100 includes a connector 157 for connecting monitoringequipment 145. The monitoring equipment may be used, for example, tomonitor temperature or pressure at the distal end of the catheter 100.As indicated above, the monitoring equipment 145 may be integrated in asingle system that also provides the controller 133 and signal processor127.

To aid in positioning the treatment member 103 of the catheter 100inside a patient's body, various marker bands (not shown) can also bedisposed at the distal and proximal ends of the catheter 100. The markerbands may be radio-opaque when the catheter is viewed by x-ray or otherimaging techniques.

Other variations in the catheter 100 are contemplated. For example, themonitoring equipment 145 is shown separately in FIG. 1, but in someimplementations, displays associated with the monitoring equipment areincluded in the user interface 130. The controller 133 is depicted ascontrolling valves 136 and 139 to regulate the flow of cryogenic fluidto the balloon 103 and channeling exhaust from the balloon 103, butother control schemes (e.g., other valves or pumps) can also beemployed. Electrodes can be arranged in ways other than shown in FIG. 1.A guidewire may be arranged differently than shown, and may beseparately controlled from the balloon portion of the catheter.Moreover, in some implementations, a guidewire may not be used.

FIGS. 2A-2D illustrate additional details of internal structures of theballoon 103 that can deliver cryotherapy. FIG. 2A shows a longitudinalcross-section of the example cryotherapy balloon 103 and an exampleelongate member 109 through which cryogenic fluid and exhaust may becycled to and from an internal chamber 215 of the cryotherapy balloon103. As shown in FIG. 2A, cryogenic fluid may be delivered from anexternal source (e.g., 121 in FIG. 1) to a cooling chamber 215 internalto the balloon 103 via a coolant delivery lumen 212. In someimplementations, an exhaust lumen 224 may be defined generally by theouter layer of the elongate shaft 109, as shown. In otherimplementations, the catheter may include one or more dedicated exhaustlumen structures (not shown) that are defined independently of theelongate member 109.

The coolant may be released into the cooling chamber 215 from an openingat the end of the delivery lumen 212, or the coolant may be releasedthrough a cryotherapy device 219 or 239 (see FIGS. 2C and 2D) disposedat the end of the delivery lumen 212. In some implementations, thecooling device 219 includes a coiled extension 235 having a number ofapertures 237 from which pressurized liquid coolant can escape andchange state to a gas.

The cooling device can take other forms. For example, as shown in FIG.2D, a cooling device 239 may include multiple coolant delivery lumens242 and 245, each with a corresponding aperture 248 and 251 throughwhich coolant can be released. Such a design can permit coolant to bereleased in a directional manner. For example, if coolant is onlydelivered through the lumen 242, and not through the lumen 245, coolingcan be concentrated in the upper half of the balloon 103. Two separatecooling lumens are shown, but more than two can be provided. Forexample, with four coolant lumens, cooling within one or more specificcircumferential quadrants may be possible, depending on which lumenscarry the coolant. In devices having multiple cooling lumens, the readerwill appreciate that the controller 133 could control multiple cryogenicfluid supply valves to precisely control regions of cooling.

In some implementations, the coolant undergoes a phase change within thecooling chamber 215, cooling the chamber 215 via the Joule-Thomsoneffect, as well as cooling the external surface 118 of the outermostballoon 103 and a patient's body tissue that is adjacent to the externalsurface 118 of the outer balloon. The cryogenic fluid, or gas if thefluid has undergone a phase change, is then exhausted through theexhaust lumen 224 to a reservoir, pump or vacuum source external to thecatheter (e.g., 124 in FIG. 1). In some implementations, there is acontinuous cycle of cryogenic fluid to the cooling chamber 215 via thedelivery lumen 212 and exhaust from the cooling chamber 215 via theexhaust lumen 224.

The coolant that is cycled into the chamber 215 is one that will providethe appropriate heat transfer characteristics consistent with the goalsof treatment. In some implementations, liquid N2O may be used as acryogenic coolant. When liquid N2O is used, it may be transported to thecooling chamber 215 in the liquid phase where it changes to a gas at theend of the coolant delivery lumen 212, or from the apertures 237 of acooling device 219. Other implementations may use Freon, Argon gas, andCO2 gas, or other agents as coolants.

In some implementations, as shown, a second balloon 221 is providedwithin the outer balloon 103 to isolate the cryogenic fluid within thecooling chamber 215. In these implementations, the outer balloon 103forms a safety chamber that prevents coolant from escaping if thecooling chamber 215 balloon 221 bursts. A separate vacuum lumen (notshown) may be provided to evacuate any gas or liquid that escapes fromthe internal cooling chamber 215; alternatively, any gas or liquid thatbreaches the second balloon 221 but not the second balloon 103 may stillbe exhausted through the exhaust lumen 224. In operation, the outer andinner balloons 103 and 221 may expand and deflate together. In someimplementations, release of coolant inflates the balloons 103 and 221.In some implementations, the balloons 103 or 221 are first inflated bythe injection of an inflation fluid or gas (e.g., a saline solution oran inert gas), after which the coolant may be introduced to the coolingchamber 115.

FIG. 2B shows a radial cross-section along the line A-A that is shown inFIG. 2A. In over the-wire implementations, the cryotherapy catheter 100includes a guidewire lumen 213, which allows the balloon 103 to berouted to a treatment site inside a patient over a pre-positionedguidewire. As shown in FIG. 2B, the coolant delivery lumen 212 isadjacent to the guidewire lumen 213, and the guidewire lumen 213 isshown to be substantially coaxial with the exhaust lumen 224, whichcorresponds to the overall shaft (e.g., elongate member 109) of thecatheter. In some implementations, lumens may have other arrangements,and more or fewer lumens may be included in the catheter. For example,the coolant delivery lumen 212 may be disposed coaxially around theguidewire lumen 213; the coolant delivery lumen 212 may be differentlydisposed within the chamber 215, such that it is not coaxial withrespect to the guidewire lumen 213 or other lumens; multiple, separatelycontrollable coolant delivery lumens may be provided; the guidewirelumen 213 may be omitted in a steerable catheter design; lumens forsteering members may be provided; one or more vacuum lumens may beincluded; one or more exhaust lumens may be included that areindependent of the outer layer of the catheter shaft 109; additionallumens may be provided for inflating or deflating the balloons 103 or221 or for inflating or deflating other balloons not shown in FIG. 2A;additional lumens may be provided to control an anchor member that maybe disposed on a guidewire near the distal portion of the balloon 103;or additional lumens may be provided to carry wires or other conductorsfor electrodes on the surface 118 of the balloon 103 (electrodes notshown in FIGS. 2A-2D).

In some implementations, the balloon 103, and a corresponding internalcooling chamber, if present (e.g., balloon 221, shown in FIG. 2A), maybe formed from a polymer including, but not limited to, polyolefincopolymer, polyester, polyethylene teraphthalate, polyethylene, polyether-block-amide, polyamide, polyimide, nylon, latex, or urethane. Forexample, certain implementations of the balloon 103 comprise PEBAX® 7033material (70D poly ether amide block). The balloon 103 may be made byblow-molding a polymer extrusion into the desired shape, or cast onto orinside of a form. In some embodiments, the balloon 103 may beconstructed to expand to a desired shape when pressurized withoutelastically deforming substantially beyond the desired shape. In someimplementations, the molding process may be modified in order to createlongitudinal splines, or thicker ridges to accommodate splines or wires,or both (splines are described in more detail below). For example, amandrel used in the molding process could be modified to have ridgescorresponding to desired splines or ridges in the balloon.

A number of ancillary processes may be used to affect the materialproperties of the balloon 103. For example, the polymer extrusion may beexposed to gamma or electron beam (e-beam) radiation which alters thepolymer infrastructure to provide uniform expansion during blow moldingand additional burst strength when in use. In addition, the moldedballoon 103 may be exposed to a low temperature plasma field andoxidizing atmosphere, which alters the surface properties to provideenhanced adhesion characteristics. Those skilled in the art willrecognize that other materials and manufacturing processes may be usedto provide a balloon portion 103 suitable for use with the catheter.

FIG. 3 is a perspective view of the cryotherapy balloon 103,illustrating additional example details of the electrodes 112 disposedon its surface 118. In some implementations, as depicted in FIG. 3, theelectrodes 112 are disposed in regular array. More particularly, forexample, the electrodes can be disposed at regular intervals alonglongitudinal lines along the surface of the balloon, such that when theballoon is inflated and in contact with body tissue, biopotentialsignals can be measured at points along a regularly spaced grid. Inother implementations, the electrodes are distributed in a differentmanner. For example, as described in greater detail with reference toFIGS. 6A and 6B, the electrodes may be staggered and disposed on only aportion of the balloon 103.

In some implementations, the electrodes are integral to the balloonsurface (e.g., molded into the balloon material itself). In otherimplementations, the electrodes may be attached to the surface of theballoon by various methods. In still other implementations, as describedin greater detail below, the electrodes may be mounted to otherstructures, such as splines or ribbons that are adjacent to or attachedto the balloon.

FIG. 4 illustrates additional detail of the example electrodes 112 shownin FIG. 3. In this particular example, the electrodes are disposed onmultiple splines, four of which are visible, and the splines are shownat an example treatment site inside a body cavity (e.g., the ostium 402of a pulmonary vein 405 (shown in a partial cut-away view) inside apatient's heart). For purposes of explanation, the visible splines inFIG. 4 are labeled as A, B, C and D. Each spline is shown with eightelectrodes 112, which are labeled as E1-E8. The arrangement depicted ismerely exemplary (e.g., in which the splines are disposedlongitudinally, relative to an axis that is common to the balloon 103and elongate member 109), and other arrangements are contemplated. Forexample, a catheter may include a greater or fewer number of splines(e.g., four, six, eight, ten, etc.), and each spline may have a greateror fewer number of electrodes (e.g., four, five, eight, ten, etc.).

In some implementations, differential biopotential measurements are madebetween pairs of adjacent electrodes on any given spline. For example,one biopotential measurement can be made across electrodes E1 and E2 onspline D; a second biopotential measurement can be made acrosselectrodes E2 and E3; a third measurement can be made across E3 and E4,and so on. By measuring biopotentials at various pairs of electrodesover time, an electrical “map” can be created to characterize andvisually depict electrical activity in tissue that is in contact withthe electrodes. In other implementations, electrodes can be employed ina unipolar, or modified differential mode, in which the potential fromone or more electrodes is measured relative to single common electrode(e.g., a reference electrode disposed at some location on the catheter),or relative to an average value of some or all of the other electrodes.Several examples of how the electrodes can be used to characterizeelectrical activity are now described with continued reference to FIG. 4and reference to FIG. 5.

In a first example, the electrodes are employed to detect a electricalsignal (“electrical signal I”) that propagates parallel to the length ofthe pulmonary vein (and along the longitudinal axis of the splines). Asdepicted in FIG. 5A, the electrical signal I is initially detected byelectrodes E1 and E2 on splines B, C and D at nearly the same time. Overtime (represented by the x-axis in FIGS. 5A-5D), the signal is detectedsubsequently at electrode pair E2-E3, then pair E3-E4, then at pairE4-E5, then at pair E5-E6. Again the signal is seen on correspondingpairs of splines B, C and D at substantially the same time, given thatthe signal is propagating parallel to the splines.

Information about electrical signals, such as that shown in FIGS. 5A-5D,can be displayed in the user interface 130 (e.g., a set of graphicaldisplays on a flat panel display that are configured to providegraphical and other information for electrically characterizing bodytissue). In some implementations, the electrical characterizationinformation includes static screen captures of biopotential informationat different points in a particular region of body tissue (e.g., pointscorresponding to electrodes on the inflatable balloon 103); theinformation can include animations illustrating time-varyingbiopotential information; the information can include color-codedisochronal or isopotential information; the information can incorporateother information previously obtained (e.g., previous electricalphysiology studies of patient, previously obtained x-rays or MRI images,etc.), or contemporaneously obtained with other equipment (e.g., imagingequipment that is employed during the cryotherapy procedure); etc.

FIG. 5B illustrates another example electrical signal (“electricalsignal II”) that propagates along the circumference of the pulmonaryvein and in a direction transverse to the splines. In this example, theelectrical signal is first detected by electrode pair E3-E4 on spline B,then on electrode pair E3-E4 on spline C, then on electrode pair E3-E4on spline D. As depicted in FIG. 5B, the delay between when the signalis respectively detected on splines B, C and D indicates that theelectrical signal I is traveling circumferentially, rather than over alarge area of the length the pulmonary vein, as in the case with theelectrical signal I depicted in FIG. 5A.

FIG. 5C illustrates another example electrical signal (“electricalsignal III”) that propagates both circumferentially and longitudinallyalong the pulmonary vein. In this example, the electrical signal isfirst detected primarily by electrode pair E2-E3 of spline B andsecondarily by electrode pair E2-E3 of spline C. Next, it is detected bythe electrode pair E3-E4 of spline C, followed by electrode pair E4-E5of spline C. Finally, the signal is detected by electrode pair E4-E5 ofspline D.

A final example is provided in FIG. 5D in which no substantialelectrical activity is detected at any electrode pairs on any of thesplines depicted. This example may correspond to a pulmonary vein thathas been treated (e.g., ablated) to eliminate aberrant electrical signalsources or pathways that may be giving rise to or contributing to anadverse condition, such as atrial fibrillation. This example may alsocorrespond to normal tissue that does not require treatment.

Disposing electrodes directly on the surface of a treatment member, suchas a cryotherapy balloon, may give rise to significant advantages. Inparticular, for example, the electrodes can facilitate mapping andcharacterization of electrical signals, as depicted in FIGS. 5A-D,before, during and after treatment—without requiring the balloon 103 tobe moved, and without requiring a separate catheter to be employed formapping. Procedures involving a single catheter that can both map andprovide cryotherapy treatment can reduce risks to the patient associatedwith switching catheters mid-procedure or employing multiple cathetersduring the procedure. In addition, electrical characterization can bevery accurate, since the electrodes may not move much (if at all) duringa cryotherapy procedure. Accordingly, the electrical characterizationbefore, during and after the procedure can accurately relate to the sameregion of tissue. Moreover, a patient can benefit from a catheter thatpermits electrical characterization of tissue during cryomapping, inwhich the tissue is only temporally treated. If the electricalcharacterization indicates that desirable electrical changes result fromcryomapping, the cryotherapy can be continued at colder temperaturesand/or for longer times (without moving the balloon 103). Conversely, ifelectrical characterization indicates that desirable electrical changesdo not result from cryomapping at a particular region of tissue,permanent treatment of that region can be avoided, limiting the tissuethat is permanently remodeled to only that tissue which providesaberrant electrical pathways or sources or electrical energy.Directional therapy, which may be possible with individual directionalcoolant lumens, such as lumens 242 and 245 shown in FIG. 2D, may also bepossible with cryotherapy balloon catheters having electrodes disposedon the expandable surface of the balloon, and the direction in whichcryotherapy is directed can be determined based on which electrodes pickup abnormal electrical signals.

In some implementations, electrodes are disposed on the surface of theballoon portion 103 of the catheter, but they may be distributeddifferently than as depicted in the examples of FIG. 3 and FIG. 4. Inparticular, for example, as shown in FIG. 6A, the electrodes may bedisposed primarily in the distal hemisphere of the balloon. Such anarrangement can be advantageous, since, in many implementations (such asthose in which the ostium of a pulmonary vein or other body lumen orcavity is treated), only that portion of the balloon comes into contactwith body tissue. In addition, with reference to FIGS. 6A and 6B, theelectrodes may be staggered, rather than having a regular spacing alonglongitudinal lines. Such a staggered arrangement can be particularlyadvantageous with electrodes have a three-dimensional structure, toprevent the electrodes from bunching up when the balloon is in acollapsed arrangement (e.g., during insertion to and extraction from thetreatment site).

As described above, the electrodes are, in some implementations,disposed on splines. FIG. 7 and following illustrate various aspects ofexample splines 701A-D. As depicted in FIG. 7, the splines 701A-D can bea separate structure that surrounds the balloon portion 103 of thecatheter. The splines 701A-D may or may not be attached to the surfaceof the balloon 103. (In FIG. 7, the splines are depicted as not beingattached). When the balloon 103 is inflated, the splines 701A-D canconform to the shape of the balloon 103, and when the balloon 103 isdeflated and withdrawn into an introducer sheath 704, the splines 701A-Dcan help deflate the balloon 103. In implementations in which thesplines 701A-D are attached to one or more points on the surface of theballoon 103, the splines 701A-D may also help inflate the balloon 103.FIG. 7 illustrates four splines 701A-D, but as mentioned above, othernumbers of splines are possible and contemplated.

The splines 701A-D can be constructed of various materials and havevarious shapes. For examples, splines can be made of Nitinol, springsteel, plastic, or some other polymer. The splines can have a roundcross section (such as a wire), a rectangular cross section (such as aribbon), or some other cross section, additional examples of which areillustrated in FIGS. 9A-9D. Moreover, the splines can be configured tohave a particular shape when released (e.g., to help shape the balloon).For example, splines constructed from spring steel or a plastic withmemory can have a natural bias in a shape that is therapeuticallyeffective (e.g., a spherical “onion” shape; a slightly pointed “turnip”shape; a tapered “carrot” shape; a curved “banana” shape; or some othershape that useful in treating a particular part of the body). In someimplementations, the splines can be biased inward, to assist indeflating the balloon, and the balloon itself can be constructed to havea particular therapeutically effective shape.

FIG. 8 illustrates an additional structural feature that can be includedin splines 701A and 70IB to enable them to help deflate and collapse theballoon 103. In particular, the proximal edge of the spline 701A caninclude a ridge or protrusion 806 that cooperates with an angled surface809 in an introducer sheath 704 of the catheter 100, such that as theballoon 103 is withdrawn into the introducer sheath 704, the angledsurface 809 exerts additional force on the protrusion 806—andcorrespondingly, on the spline 701A—to help collapse the balloon 103.This is just one example structure, but the reader will appreciate thatvarious other designs can be employed to exert pressure on the splinesto enable them to more effectively deflate the balloon or prevent theballoon from bunching up or snagging as it is refracted into the sheath704.

FIGS. 9A-9C illustrate various additional cross-sections of examplesplines. As shown in FIG. 9A, the spline 901 may have a ribbon shapewith a channel 904 at the top for carrying wires to electrodes disposedon the spline (described in greater detail below), or for carrying aspring wire. In implementations that include a spring wire, the ribbonshape of the spline can distribute the pressure exerted by the springwire across a larger area, which may minimize the risk of damage to theballoon. FIG. 9B illustrates an arc-shaped spline 907, that may providegreater strength in one particular direction (e.g., the arc may exert agreater force in the radial direction than other shapes). FIG. 9Cillustrates an example spline 910 that is primarily circular incross-section with a groove 913 (e.g., to carry wires for electrodesdisposed on the spline and/or a spring wire).

As described above, the splines can be disposed around and adjacent tothe balloon. In other implementations, splines may be more integral tothe balloon 103, such as the example splines 1001. For example, withreference to FIG. 10—a cross section along lines D-D of the balloon 103that is shown in FIG. 3—the outer balloon 103 may be constructed to haveridges or grooves 1002 that accommodate the splines 1001. In someimplementations, the balloon material is thicker near the ridges orgrooves, as depicted by the regions 1005. The regions 1005 of thickerballoon material may provide the spline functionality themselves,without an external, rigid spline structure 1001; or, as shown, theregions 1005 can accommodate a separate spline 1001. In someimplementations, a groove in each region of thicker material 1005 canaccommodate electrodes and corresponding wires in place of, or inaddition to, splines. Other example structures are shown for referencein FIG. 10, including, for example, the inner balloon 221, guidewirelumen 213 and coolant delivery lumen 212.

Various example electrodes and corresponding wiring schemes for theelectrodes are now described with continued reference to the figures.FIG. 11A illustrates one example electrode construction in whichelectrodes are formed from insulated wire 1102 that is made from abiocompatible material (e.g., platinum-coated copper) by stripping theinsulation away at appropriate points. In particular, for example, asshown in FIG. 11A, electrodes 1105 can be formed by stripping theinsulation away at corresponding regions 1108. When the wires are incontact with body tissue, electrical contact can be made between theexposed wires at the regions 1108. In some implementations, the wiresare, in size, on the order of 40 AWG (American wire gauge). FIG. 11A ismerely exemplary, and other configurations are contemplated. Forexample, two conductors 1109 and 1110 are depicted in FIG. 11A, but awire may have more conductors to provide a greater number of electrodecontacts (e.g., four, six, eight, etc.). Moreover, the wires are shownas having a substantially circular cross-section and being individuallyinsulated with substantially circumferential insulators, but othertopologies are contemplated (e.g., rectangular or arc-shaped conductorsthat may provide spline functionality in addition to conductingelectrical signals).

FIG. 11B illustrates another variation in which raised beads 1112 can beincluded to facilitate better contact between adjacent tissue (notshown) and exposed wires. As described above with reference to FIGS. 6Aand 6B, and as depicted in FIG. 11B, the electrode beads 1112 can bestaggered to prevent the electrodes from bunching up when the balloon onwhich they are disposed is collapsed. Staggering the electrodes as showncan also minimize the chance that adjacent electrodes will shorttogether when the balloon 103 is deployed inside a patient.

FIG. 11C illustrates another variation in which electrode rings 1115 canbe included in the wires. In some implementations, electrode rings 1115completely or substantially cover the circumference of a portion of acorresponding wire 1118, and can promote solid electrical contactbetween conductor(s) internal to the wire and adjacent tissue,regardless of the orientation of the wire when it is deployed with theballoon catheter.

FIGS. 12A-12D illustrate another example spline and electrode structure.In particular, splines 1202 can be formed from a sheet 1205 of thinmaterial, such as, for example, Kapton™. More particularly, slits 1208can be made in the sheet 1205 of the material, such that the sheet 1205can be formed into a cylinder or sphere and wrapped around and affixedto the outer surface a balloon 103, as depicted in FIG. 12B.

Electrical traces and electrodes can be formed on the flexible sheet1205 of material as depicted in FIG. 12C. In particular, a conductor1211 can be disposed on the flexible sheet 1205 of material and coveredwith insulation 1213, which can be selectively removed to formelectrodes. For example, FIG. 12C illustrates two example tracesdisposed on the flexible sheet 1205 (e.g., Kapton™). As depicted, thetraces include a layer 1215 of a first material (e.g., copper), which iscoated by a layer 1217 of a second material (e.g., platinum), thencovered with an insulator 1213. Two conductor layers may be advantageousin some implementations to promote strength, good electricalconductivity, and biocompatibility, and a copper-platinum combinationmay be particularly advantageous. Other implementations employ only asingle conductor layer. To manufacture such electrodes and wires, theinsulator 1213 can be selectively applied and removed, for example,using lithography and photo resists, or other appropriate techniques, ascan the conductor layer(s) themselves.

FIG. 12D illustrates an example cut-away view of a two-layertrace/electrode structure in which conductor layers 1220 and 1222 aredisposed on both sides of the flexible sheet 1205 and selectivelyinsulated with insulator layers 1225 and 1228 that is not applied in aregion 1230 to form an electrode. In a two-layer implementation, aconnection can be made through an opening (not shown) in the flexiblesheet 1205 in order to connect conductors on one layer to conductors onthe other layer, much like an electrical through-connection (e.g., avia) on a printed circuit board. Two-layer implementations may beadvantageous where there are large number of electrodes, in order todispose the electrodes on the layer of the flexible sheet 1205 thatcomes into contact with body tissue and to run signal paths to eachelectrode on the opposite side of the flexible sheet, where the signalpaths may be more protected and less prone to break or becomeelectrically open.

However the electrodes and wires are configured on the surface of theballoon 103, wires from the balloon can be routed to the proximal end ofthe catheter in various ways. For example, in some implementations, oneor more dedicated lumens are employed to route individual electrodewires through the catheter shaft 109. In another implementation, asdepicted in FIG. 13, wires 1302 may be used for a secondary purpose,such as strengthening the catheter shaft 109. In particular, forexample, the wires can be embedded in the catheter shaft 109 in the formof a braid, as shown. At the distal end of the catheter shaft 109,individual wires from the braid can be separated out and routed toappropriate electrodes (e.g., electrode 1305) on different splines(e.g., splines 1301-1304).

FIG. 14 is flow diagram of an example method 1400 of ablating bodytissue with the cryotherapy catheter 100 that is described above. Theinflatable balloon portion 103 can be located (1401) at a treatment siteinternal to a patient. For example, the distal balloon portion 103 canbe disposed in a patient's left atrium in order to treat, withcryotherapy, atrial fibrillation resulting from aberrant electricalpathways in the patient's pulmonary veins. More particularly, theballoon 103 can be disposed in the ostium 402 one of the patient'spulmonary veins, as depicted in FIG. 4.

Electrodes on the surface of the balloon 103 can be employed toelectrically characterize (1404) body tissue at the treatment site. Forexample, the electrodes 112 (and more particularly, the electrodes E1-E8on each of splines A-D shown in FIG. 4) can be sampled by the signalprocessor 127 (see FIG. 1). The signal processor can analyze sampledbiopotential values from the electrodes and provide output that enablesa medical professional to, for example, identify aberrant electricalpathways in body tissue at the treatment site. The output can include,for example, graphical representations of the biopotential values atdifferent points in time and presented in a manner that illustratesspatial relationship between different biopotential values, as depictedin FIGS. 5A-5D.

If the electrical characterization at action 1404 indicates that thebody tissue being characterized is a candidate for ablation (decisionbox 1407), the tissue can be cooled (1410) to a temporarily therapeuticvalue (e.g., to a particular temperature, such as 0° C., or for aparticular duration of time, such as 30 seconds or one minute). If thetissue is not a candidate for ablation, the inflatable balloon 103 canbe repositioned at another region of tissue. Tissue (e.g., pulmonaryvein tissue) may be a candidate for ablation when it unexpectedlypropagates or generates electrical signals. More particularly, forexample, tissue having an electrical characterization like that shown inFIG. 5A, 5B or 5C may be a candidate for ablation when an electricalcharacterization like that shown in FIG. 5D is expected. Cooling to atemporarily therapeutic value can include cryomapping the tissue (e.g.,only mildly cooling or freezing the tissue, rather than freezing thetissue to a very low temperature). With reference to the overallcryotherapy catheter 100, cryomapping the tissue can include deliveringan amount of cryogenic fluid to the chamber 215 of the inflatableballoon 103 (and exhausting an appropriate amount of the resulting gas)that results in the surface 118 of the balloon reaching a temperatureappropriate for cryomapping, for an appropriate duration of time.

Once the tissue is cooled to a temporary therapeutic temperature, thetissue can again be electrically characterized (1413), as describedabove. If a reduction in undesirable electrical activity is observed(decision box 1416), the body tissue can be cooled (1419) to a lower,permanently therapeutic temperature. For example, if the initialelectrical characterization of a particular region of body tissue is asshown in FIG. 5A, and electrical characterization of the temporarilycooled tissue is as shown in FIG. 5D, the temporary cooling may revealthat permanent ablation of the tissue is appropriate. In such a case, anadditional volume of cryogenic fluid, for an additional time, can bedelivered to the chamber 215, in order to cryo ablate the tissue. On theother hand, an unchanged electrical characterization of a particularregions of tissue (e.g., an electrical characterization as shown in FIG.5 A, both before and after temporary cooling of the tissue) may indicatethat the tissue being characterized is not the source of the undesirableelectrical activity, and it may be more appropriate to reposition (1401)the inflatable balloon 103 at another region of tissue.

When tissue is treated, a sufficient volume of cryogenic fluid can beapplied for a sufficient time to, for example, cool tissue to −20° C. orcooler, at a therapeutic depth (e.g., the thickness of the vessel orstructure being treated, which in some cases may be 1-5 mm). In someimplementations, appropriate cooling can be applied by delivering enoughcryogenic fluid to the balloon to cool the external surface of theballoon to −60° to −90° C. for a period of time in the range of one toten minutes. These values are exemplary, and the reader will appreciatethat the volume of cryogenic fluid delivered and the time of deliverycan be selected to achieve appropriate therapy goals in view ofcharacteristics of the body tissue being treated.

Once treated, tissue can again be electrically characterized (1425),after it has warmed up (1422) enough to permit accuratecharacterization. In some implementations, the tissue is allowed to warmup to its nominal temperature (e.g., 37° C. for a human patient); inother implementations, the tissue may be characterized after it reachesa temperature that is higher than a cryomapping temperature, but beforeit reaches its nominal value. In some implementations, the flow ofcryogenic fluid to the inflatable balloon 103 is stopped (or reduced toa rate that allows the balloon 103 to remain inflated but does notextract heat from the adjacent tissue), and the tissue is allowed towarm up on its own (e.g., through metabolism in cells of the treatedtissue or tissue that is in thermal contact with the heated tissue,conduction of heat from tissue or blood that is in thermal contact withthe treated tissue, etc.). In other implementations, a warming fluid(e.g., warm saline) may be injected into the balloon 103 to acceleratethe warming process (1422).

If a reduction in undesirable electrical activity is observed (decisionbox 1428) following permanent treatment (1419) of the tissue, theballoon 103 can be repositioned (1401) at another treatment site, if oneexists (decision box 1431); or the balloon 103 can be deflated andremoved (1434) from the patient. If, on the other hand, an insufficientreduction in undesirable electrical activity is observed (decision box1428), the cooling process 1419 can be repeated. In someimplementations, even if the electrical characterization 1425 indicatesa satisfactory reduction in undesirable electrical activity, the coolingprocess may be repeated a second time to increase the chances that theprocedure will be effective over a long period of time.

The method 1400 is described above and in this document with primaryreference to treating tissue of pulmonary veins of a patient in order totreat atrial fibrillation; however, the method can be employed in otherregions of a patient to treat any other conditions, such as otherconditions that benefit from cryotherapy and that may further benefitfrom electrical characterization of the tissue to be treated by thecryotherapy. Variations of the method 1400 are contemplated. Forexample, in some cases, actions in the method 1400 may be skipped orperformed in a different order. In particular, for example, tissue maybe immediately ablated by being cooled to a permanently therapeutictemperature, without intermediate actions and decisions 1410, 1413 and1416 being performed. Moreover, tissue may be electrically characterizedwhile it is being cooled, rather than in sequence with the cooling, orcharacterized at times other than those depicted in FIG. 14. Othervariations are possible.

A number of implementations have been described. Nevertheless, it willbe understood that various modifications may be made without departingfrom the spirit and scope of this document. Accordingly, otherimplementations are within the scope of the following claims.

What is claimed is:
 1. A device, comprising: a catheter having a distalend, a proximal end and a longitudinal axis extending therebetween; aballoon coupled to the distal end of the catheter; and a plurality ofseparate flexible electrode assemblies circumferentially spaced apartfrom each other and attached to an outer surface of the balloon, eachelectrode assembly comprising a flexible sheet, first and secondconductor layers extending longitudinally along opposing first andsecond surfaces of the flexible sheet, and first and second insulatorlayers disposed over at least a portion of the first and secondconductor layers, respectively; wherein at least one of the flexibleelectrode assemblies includes a first electrode formed by an opening inthe first insulator layer and a second electrode formed by an opening inthe second insulator layer, wherein the first and second electrodes arespaced apart longitudinally from each other.
 2. The device of claim 1,wherein the first and second conductor layers include copper.
 3. Thedevice of claim 1, wherein the first and second conductor layers includeplatinum.
 4. The device of claim 1, wherein the first and secondconductor layers each include a layer of a first material coated with alayer of a second material different from the first material.
 5. Thedevice of claim 4, wherein the first material is copper and the secondmaterial is platinum.
 6. The device of claim 1, further comprising athermal sensor.
 7. The device of claim 1, further comprising a sheaththat surrounds the catheter, through which the catheter is translated.8. The device of claim 1, wherein wires connected to the electrodesextend along the catheter in a braided pattern towards the proximal end.9. A device, comprising: an elongate shaft having a distal end, aproximal end and a longitudinal axis extending therebetween; a ballooncoupled to the distal end of the elongate shaft; and a plurality ofseparate flexible electrode assemblies circumferentially spaced apartfrom each other and attached to an outer surface of the balloon, eachelectrode assembly comprising a first insulator layer disposed on theballoon, a first conductor layer disposed on the first insulator layer,a flexible sheet disposed on the first conductor layer, a secondconductor layer disposed on the flexible sheet, and a second insulatorlayer disposed on the second conductor layer; wherein at least one ofthe flexible electrode assemblies includes a first electrode formed byan opening in the first insulator layer and a second electrode formed byan opening in the second insulator layer, wherein the first and secondelectrodes are spaced apart longitudinally from each other.
 10. Thedevice of claim 9, wherein the first and second conductor layers includecopper.
 11. The device of claim 9, wherein the first and secondconductor layers include platinum.
 12. The device of claim 9, whereinthe first and second conductor layers each include a layer of a firstmaterial coated with a layer of a second material different from thefirst material.
 13. The device of claim 12, wherein the first materialis copper and the second material is platinum.
 14. The device of claim9, further comprising a thermal sensor.
 15. The device of claim 9,further comprising a sheath that surrounds the elongate shaft, throughwhich the elongate shaft is translated.
 16. The device of claim 9,wherein wires connected to the electrodes extend along the elongateshaft in a braided pattern towards the proximal end.
 17. A device,comprising: a catheter having a distal end, a proximal end and alongitudinal axis extending therebetween; a balloon coupled to thedistal end of the catheter; and a plurality of separate flexibleelectrode assemblies circumferentially spaced apart from each other andattached to an outer surface of the balloon, each electrode assemblycomprising a flexible sheet with first and second electrodes disposed onfirst and second opposing surfaces of the flexible sheet, respectively,wherein the first and second electrodes are spaced apart longitudinallyfrom each other.
 18. The device of claim 17, wherein first and secondconductor layers extend longitudinally along the first and secondsurfaces of the flexible sheet, and first and second insulator layersare disposed over at least a portion of the first and second conductorlayers, respectively.
 19. The device of claim 18, wherein the firstelectrode is formed by an opening in the first insulator layer and thesecond electrode is formed by an opening in the second insulator layer.20. The device of claim 17, wherein the first and second conductorlayers each include a layer of a first material coated with a layer of asecond material different from the first material.